We are obtaining genome sequence data on 235 Pima Indians, each from a different nuclear family. Among these individuals, 208 had been studied as inpatients in our CRC when they were non-diabetic, and are informative for percent body fat, glucose and insulin responses during a 2hr oral glucose tolerance test, measures of insulin stimulated glucose uptake (clamp), acute insulin response to an intravenous glucose bolus (N=170), and measures of 24hr energy expenditure in a respiratory chamber (N=146). Some had undergone skeletal muscle biopsies (N=83) or subcutaneous abdominal adipose biopsies (N=73). Also among the 235 subjects, 29 individuals had onset age of T2D <25 years, 52 had onset age <30 years, and 31 were non-diabetic as of their last exam at which time they were aged >40 years. Genome sequencing and alignment was outsourced to Complete Genomics Institute (CGI; 35 genomes) or Illumina (200 genomes). The data was received from CGI in Oct 2012 and Illumina in March 2013. Genotype calling and variant annotation is being performed in my lab by using GATK (Broad Institute). Association analysis in the 235 samples and in silico prediction programs will be used to prioritize variation for follow-up.